Evidence clearly indicates that the Group A streptococcus is the etiological agent in rheumatic fever, but its role in the pathogenesis of this disease remains obscure. Cell-mediated immunity (CMI) as well as humoral immunity appears to play a significant role in the pathogenesis of a variety of inflammatory diseases. As CMI may also be involved in the pathogenesis of rheumatic carditis, the specific aims of this research project are: 1) localization of cross-reacting antigens for cell-mediated immunity at the subcellular level of myocardium and Group A streptococcus; 2) comparison of the response of lymphoid cells from BALB/c mice to myocardial and Group A streptococcus antigens; 3) induction of lymphoid cells which are cytotoxic to heart cells in culture; 4) in vivo production of myocardial lesions by passive transfer of sensitized lymphocytes; 5) in vivo production of myocardial lesions by immunization with streptococcal antigens; 5a) temporal development of these lesions; 5b) correlation with state of cellular immunity. This will be accomplished by sensitizing BALB/c mice with heat-killed Group A streptococci and subcellular antigens. Cross-reactions between these antigens and cardiac antigens will be assayed for by lymphocyte stimulation, production of macrophage inhibition factor, and cytotoxicity as measured by 51 chromium release and histologic examination. This project proposes to tie together some of the fragmentary evidence now in the literature concerning CMI in streptococcal disease and post-streptococcal rheumatic carditis.